The myriad of chemical dump sites identified in the United States and in most industrialized countries represent a potential continuing threat to the environment and to human health. Hazardous chemical wastes are highly complex mixtures not readily amenable to conventinal chemical analysis. This proposal will develop and validate short term in vitro bioassays for the detection and quantitation of toxic halogenated aromatics such as the polychlorinated dibenzo-p-dioxins (PCDDs), biphenyls (PCBs), dibenzofurans (PCDFs0 and related compounds. For several classes of halogenated aromatics there appears to be a correlation between the toxicity of individual compounds and their (biological) activity as microsomal AHH inducers and as competitors for a cytosolic receptor protein. Both bioassays will be adapted for rapid routine screening of complex chemical mixtures for potentially toxic halogenated aromatics (e.g. 2,3,7,8-TCDD). The receptor binding assay and the AHH indication assay (using rat hepatoma cells) will be assessed and validated using individual PCB, PCDD and PCDF congeners, reconstituted mixtures and organic extracts from commercial chlorinated phenols, fly ash and dump sites. The activities of the mixture will be expressed in terms of pg or pmol equivalents of 2, 3, 7, 8-TCDD and the correlation between the biological activity and toxicity of the mixtures will be validated using the guinea pig LD50 as a toxic end point.